Lior Rosenberg

NKp44 Receptor Mediates Interaction of the Envelope Glycoproteins from the West Nile and Dengue Viruses with NK Cells

Dengue virus (DV) and West Nile virus (WNV) have become a global concern due to their widespread distribution and their ability to cause a variety of human diseases. Antiviral immune defenses involve NK cells. In the present study, we investigated the interaction between NK cells and these two flaviviruses. We show that the NK-activating receptor NKp44 is involved in virally mediated NK activation through direct interaction with the flavivirus envelope protein. Recombinant NKp44 directly binds to purified DV and WNV envelope proteins and specifically to domain III of WNV envelope protein; it also binds to WNV virus-like particles. These WNV-virus-like particles and WNV-domain III of WNV envelope protein directly bind NK cells expressing high levels of NKp44. Functionally, interaction of NK cells with infective and inactivated WNV results in NKp44-mediated NK degranulation. Finally, WNV infection of cells results in increased binding of rNKp44 that is specifically inhibited by anti-WNV serum. WNV-infected target cells induce IFN-γ secretion and augmented lysis by NKp44-expressing primary NK cells that are blocked by anti-NKp44 Abs. Our findings show that triggering of NK cells by flavivirus is mediated by interaction of NKp44 with the flavivirus envelope protein.

Proliferating Cell Nuclear Antigen Is a Novel Inhibitory Ligand for the Natural Cytotoxicity Receptor NKp44

NK cells play an important role in the early immune response to cancer. The NKp44 activating receptor is the only natural cytotoxicity receptor that is expressed exclusively by primate NK cells, yet its cellular ligands remain largely unknown. Proliferating cell nuclear Ag (PCNA) is overexpressed in cancer cells. In this study, we show that the NKp44 receptor recognizes PCNA. Their interaction inhibits NK cell function through NKp44/ITIM. The physical interaction of NKp44 and PCNA is enabled by recruitment of target cell PCNA to the NK immunological synapse. We demonstrate that PCNA promotes cancer survival by immune evasion through inhibition of NKp44-mediated NK cell attack.

Early outcome and complications of the extended subcranial approach to the anterior skull base

Objectives: To present the technique of the extended subcranial approach to the anterior skull base and to review the results in 55 patients who underwent the procedure. Study Design: Retrospective review of the records of 55 patients who underwent the extended subcranial approach to the anterior skull base between 1994 and 1998 for the treatment of various neoplasms originating in the nasal cavity, nasopharynx, paranasal sinuses, orbit, or meninges, as well as for the repair of complex craniofacial trauma and/or cerebrospinal fluid (CSF) leak. Preoperative patient evaluation and the surgical technique are also reviewed. Methods: Patient records were retrospectively reviewed and tabulated for age, sex, and indications for procedure, with special focus on early outcome and complications. Results: Twenty‐six patients underwent oncologic resections, 22 patients had reduction of complex fronto‐naso‐orbital and skull base fractures, and seven patients had repair of CSF leak. Significant complications in the oncologic group consisted of one hematoma requiring needle aspiration and two cases of temporary nontension pneumocephalus. In the fracture group, one patient died because of extensive intracerebral damage and multiorgan failure, and one patient had nontension pneumocephalus coupled with CSF leakage and one patient had temporary nontensisn pneumocephalus. The most common late complication in all three groups was anosmia. Conclusions: Based on their review, the authors conclude that the extended subcranial approach to the anterior skull base is a safe, versatile, and effective procedure for the surgical treatment of various pathological conditions involving the anterior skull base.

The S Nipple-areola Reconstruction

Nipple reconstruction is performed as a last stage in breast reconstruction following mastectomy. Various methods of nipple reconstruction have been described, most of them utilizing either free composite grafts or local flaps. The main problem encountered using either method is the gradual absorption and flattening of the nipple. The technique we used in reconstructing 22 nipples, in preference over the various methods accepted in breast reconstruction, achieves a long-standing, protruding nipple constructed from two large local flaps raised from an S-shape design. The technique is simple and permits freedom in choosing the height of the nipple, even in the presence of a mastectomy scar. The size of the nipple thereby constructed is in excess of what was expected. Shrinkage occurs during the first 2 months, and the resulting size is more than adequate. The areola is reconstructed by a full-thickness skin graft harvested from a nonhairy area of the upper inner thigh. The local flaps lack the necessary color, which is achieved by tattooing.

A graded work site intervention program to improve sun protection and skin cancer awareness in outdoor workers in Israel

AbstractObjectives: A graded worksite intervention program to improve sun protection and skin cancer awareness of outdoor workers was implemented and evaluated longitudinally over a period of 20 months. Methods: Outdoor male workers (144/213 recruits) from geographically separated units of the Israel National Water Company were allocated to complete (n = 37), partial (n = 72) or minimal (n = 35) intervention groups. Subsequent to the assignment and training of local safety officers, an educational and medical screening package was provided to the corresponding groups either once, or repeatedly a year later. Personal sun protective gear was provided upon repeated intervention. Outcome measures were evaluated through self-response questionnaires administered prior to the first intervention pulse, and 8 months after the first and second interventions. Results: A 15–61% improvement in sun-protection habits was noted in the entire study population 8 months after initialization, compared to no sunscreen use, 20% sun-exposed skin area and highest mean occupational exposure dose of 1.68 MED/day at pre-test. An even greater use of sunscreen was evident 1 year later in the complete and partial intervention groups, + 80% and + 52%, respectively. The baseline rate of self-examination of the skin in the same two groups (49%) increased significantly at post-test (+ 71% and + 53%, respectively). Conclusions: This integrated intervention program led to significantly improved sun protection and skin cancer awareness. Repeated intervention combined with the supply of sun-protective gear contributed to an even greater impact.

A novel rapid and selective enzymatic debridement agent for burn wound management: A multi-center RCT

OBJECTIVES Excisional debridement followed by autografting is the standard of care (SOC) for deep burns, but is associated with serious potential complications. Conservative, non-surgical and current enzymatic debridement methods are inefficiently slow. We determined whether a non-surgical option of rapid enzymatic debridement with the debriding enzyme NexoBrid™ (NXB) would reduce need for surgery while achieving similar esthetic and functional outcomes as SOC. METHODS We conducted a multi-center, open-label, randomized, controlled clinical trial including patients aged 4-55 years with deep partial and full thickness burns covering 5-30% of their total body surface area (TBSA). Patients were randomly assigned to burn debridement with NXB (applied for 4h) or SOC, which included surgical excisional or non-surgical debridement. RESULTS NXB significantly reduced the time from injury to complete débridement (2.2 vs. 8.7 days, P<0.0001), need for surgery (24.5% vs. 70.0%, P<0.0001), the area of burns excised (13.1% vs. 56.7%, P<0.0001) and the need for autografting (17.9% vs. 34.1%, P=0.01). Scar quality and quality of life scores were similar in both study groups as were the rates of adverse events. CONCLUSIONS Enzymatic débridement with NXB resulted in reduced need for and extent of surgery compared with SOC while achieving comparable long-term results in patients with deep burns. TRIAL REGISTRATION Clinical Trials.gov NCT00324311.

Malignant fibrous histiocytoma of soft tissue

SummaryTwo cases of malignant fibrous histiocytoma are presented. The clinicopathologic findings are also reported. The disease was of fast growing pattern and the outcome of one of the cases very rapid. The relative literature is reviewed and the histogenesis is emphasized.

Chemical burns: our 10-year experience.

A review of 173 patients with chemical burns admitted to our burn unit was carried out during the years 1976-85. Most burns were work related (83 per cent). The majority of patients were men aged 21-50 years (mean age = 29.6 years). The mean total body surface area involved was 3.6 per cent (range = 1-30 per cent). The mean length of stay in hospital was 6.3 days (range = 1-52 days). The extremities were involved in 68 per cent of the patients. The more common aetiological agents were bromine and its compounds (36 per cent), then acids (21 per cent), alkalis and organic substances (14.5 per cent each). The severest burns were caused by the inorganic substances. Delayed admission was most characteristic of the bromine and alkali burns. Complications included local infection (19 cases), systemic infection (two cases), inhalation injury (two cases), tissue necrosis (one case) and corneal erosion (one case). There were no deaths. Increased awareness of the hazardous potential of chemicals should help reduce the incidence of chemical burns.

Rapid and selective enzymatic debridement of porcine comb burns with bromelain-derived Debrase: acute-phase preservation of noninjured tissue and zone of stasis.

Deep burns are associated with the formation of an eschar, which delays healing and increases the risk of infection. Surgical debridement of the eschar is, at present, the fastest means to achieve an eschar-free bed, but the process can not differentiate between the viable tissue and the eschar and follow the minute irregularities of the interface between the two. We evaluated the efficacy and selectivity of a novel enzymatic bromelain-based debriding agent, Debrase® Gel Dressing (Debrase®), in a porcine comb burn model. We hypothesized that Debrase® would result in rapid debridement of the eschar without adverse effects on the surrounding uninjured skin. This is a prospective, controlled, animal experiment. Five domestic pigs (20–25 kg) were used in this study. Sixteen burns were created on each animals dorsum using a brass comb with four rectangular prongs preheated in boiling water and applied for 30 seconds, resulting in four rectangular 10 × 20 mm full-thickness burns and separated by three 5 × 20 mm unburned interspaces representing the zone of stasis. The burned keratin layer (blisters) was removed, and the burns were treated with a single, topical, Debrase® or control vehicle application for 4 hours. The Debrase®/control was then wiped off using a metal forceps handle, and the burns were treated with a topical silver sulfadiazine (SSD). The wounds were observed, and full-thickness biopsies were obtained at 4 and 48 hours for evidence of dermal thickness, vascular thrombosis, and burn depth, both within the comb burns and the unburned interspaces in between them. Chi-square and t tests are used for data analysis. A single 4-hour topical application of Debrase® resulted in rapid and complete eschar dissolution of all the burns in which the keratin layer was removed. The remaining dermis was thinner (1.1 ± 0.7 mm) than in the control burns (2.1 ± 0.3 mm; difference 0.9 mm [95% confidence interval: 0.3–1.4]) and was viable with no injury to the normal surrounding skin or to the unburned interspaces between the burns, which represents the zone of stasis. In control burns, the entire thickness of the dermis was necrotic. At 48 hours, Debrase®-treated areas were found partially desiccated under SSD treatment. The unburned interspaces demonstrated partial-thickness necrosis in two third and full-thickness necrosis in one third of wounds. In contrast, full-thickness necrosis was noted in all control interspaces (P = .05). In a porcine comb burn model, a single, 4-hour topical application of Debrase® resulted in rapid removal of the necrotic layer of the dermis with preservation of unburned tissues. At 48 hours, SSD treatment resulted in superficial tissue damage and partial preservation of the unburned interspaces.

Risk Factors for Incomplete Excision of Basal Cell Carcinomas

Incomplete excision of basal cell carcinomas (BCCs) may be followed by recurrence of the tumor. In order to detect risk factors for incomplete excision of BCCs we performed a cross-sectional study of 1278 patients who underwent a primary excision of BCCs, during a four-year period, within an ambulatory and hospital plastic surgery department setting. Incomplete excision occurred in 159 of 1478 primary excisions of BCCs (10.8%) and was significantly associated with location of the tumors in the eyelids (OR 3.64, 95% CI 1.96-6.71), ears (OR 2.51, 95% CI 1.25-4.94), naso-labial folds (OR 2.26, 95% CI 0.99-5.04) and nose (OR 1.88, 95% CI 1.30-2.71). There was an inverse association with location of the tumors in the upper limbs (OR 0.44, 95% CI 0.21-0.90), back (OR 0.12, 95% CI 0.02-0.48) or chest (OR 0.09, 95% CI 0.00-0.57). Baso-squamous differentiation was associated with incomplete excision of BCCs (p = 0.03). No association was observed between incomplete excision of BCCs and gender, age, setting of the operation (ambulatory vs. hospital), clinical appearance of the lesion (suspected BCCs vs. other diagnoses) or diameter of the lesions. In conclusion, incomplete excision of BCCs was associated with location of the tumors in the eyelids, ears, naso-labial folds and nose. We recommend that in patients with BCCs located in these sites, surgeons should commence particular surgical measures to avoid inadequate excisions of the tumors.